TY  - JOUR
A1  - Biedenbänder, Thomas
A1  - Jesus, Vanessa de
A1  - Schmidt-Dengler, Martina
A1  - Helm, Mark
A1  - Corzilius, Björn
A1  - Fürtig, Boris
T1  - RNA modifications stabilize the tertiary structure of tRNAfMet by locally increasing conformational dynamics
T2  - Nucleic acids research
N2  - A plethora of modified nucleotides extends the chemical and conformational space for natural occurring RNAs. tRNAs constitute the class of RNAs with the highest modification rate. The extensive modification modulates their overall stability, the fidelity and efficiency of translation. However, the impact of nucleotide modifications on the local structural dynamics is not well characterized. Here we show that the incorporation of the modified nucleotides in tRNAfMet from Escherichia coli leads to an increase in the local conformational dynamics, ultimately resulting in the stabilization of the overall tertiary structure. Through analysis of the local dynamics by NMR spectroscopic methods we find that, although the overall thermal stability of the tRNA is higher for the modified molecule, the conformational fluctuations on the local level are increased in comparison to an unmodified tRNA. In consequence, the melting of individual base pairs in the unmodified tRNA is determined by high entropic penalties compared to the modified. Further, we find that the modifications lead to a stabilization of long-range interactions harmonizing the stability of the tRNA’s secondary and tertiary structure. Our results demonstrate that the increase in chemical space through introduction of modifications enables the population of otherwise inaccessible conformational substates.
Y1  - 2022
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/75132
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-751323
SN  - 1362-4962
N1  - Chemical shifts and relaxation data are deposited at BMRB under accession code 51144.
N1  - Funding for open access charge: University Frankfurt.
N1  - Funding: HMWK
VL  - 50
IS  - 4
SP  - 2334
EP  - 2349
PB  - Oxford Univ. Press
CY  - Oxford
ER  -